title: Design, synthesis, and evaluation of coumarin-based molecular probes for imaging of myelination.
abstract: Myelination represents one of the most fundamental biological processes in the vertebrate nervous system. Abnormalities and changes in myelination in the central nervous system (CNS) are seen in many neurodegenerative disorders, such as multiple sclerosis (MS). A long-standing goal has been to directly detect and quantify myelin content in order to facilitate diagnosis and therapeutic treatments of myelin-related diseases. In the course of our studies, we have developed a series of small-molecule probes (SMP) as myelin-imaging agents. Among them are coumarin derivatives, which exhibit promising brain permeability and myelin-binding properties. Herein we report a full account of the design and synthesis of coumarin-based SMPs as myelin-imaging agents. Systematic evaluation of these SMPs in both the CNS and peripheral nervous system (PNS) allowed us to identify some lead agents for potential use as fluorescent dyes for intraoperative nerve mapping in surgical operations or as radiotracers for positron emission tomography (PET) imaging of myelination.
authors.affiliation: Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States.
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism / Q000502:physiology*; D013194:Staining and Labeling; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D015335:Molecular Probes; C030123:coumarin